title: Brief report: SRF-dependent MiR-210 silences the sonic hedgehog signaling during cardiopoesis.
abstract: Serum response factor (SRF) wields potent gene silencing activity through its regulation over numerous microRNAs (miRs). Here, SRF directs embryonic stem cell (ESC) progenitor cell lineage specification in part by silencing genes through miR-210. Viral expression of miR-210 in murine ESCs-derived embryoid bodies (EBs) inhibited cell growth and inhibited the appearance of cardiac progenitor markers Nkx2.5 and Gata4 and terminal differentiated contractile proteins Mlc2v and βMHC. Knockdown of miR-210 expression via antisense RNA activated cardiac progenitor gene activity. miR-210 inhibitory activity was attributed to silencing of the Sonic hedgehog (Shh) signaling pathway, which fosters the cardiac progenitor program. miR-210 directly silenced Shh via targeting of the Shh 3'UTR, comparable to the chemical Shh inhibitor, cyclopamine. miR-210 silencing of Shh/Gli1 signaling also blocked expression of the cell cycle regulators Cyclin D1 and Cyclin D2, and EB cell expansion. Absence of SRF expression in SRF null EBs blocked miR-210 expression, coincident with enhanced Shh, and Gli1 gene activity. Thus, SRF-dependent miR-210 expression may operate as a novel silencer of the Shh signaling pathway.
authors.affiliation: Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, USA.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zheng
authors.forename: Ye
authors.initials: Y
authors.lastname: Tao
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartz
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000502:physiology; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism; D034622:RNA Interference; D026362:Serum Response Factor / Q000502:physiology*; D015398:Signal Transduction; D000071676:Zinc Finger Protein GLI1
chemical_list: D020413:3' Untranslated Regions; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; C549325:MIRN210 microRNA, mouse; D035683:MicroRNAs; D026362:Serum Response Factor; C465570:Shh protein, mouse; D000071676:Zinc Finger Protein GLI1
keywords: Cardiac; Developmental biology; Differentiation; Embryoid bodies; Embryonic stem cells